Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

Alzheimer's disease MCI amyloid beta biomarker dementia plasma

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
28 Jun 2024
Historique:
revised: 30 03 2024
received: 29 01 2024
accepted: 02 04 2024
medline: 28 6 2024
pubmed: 28 6 2024
entrez: 28 6 2024
Statut: aheadofprint

Résumé

Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline. We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aβ42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AβX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. Our results suggest that assessing the plasma AβX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD. New plasma Aβ42/Aβ40 measurement using immunoprecipitation-immunoassay Plasma Aβ42/Aβ40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.

Identifiants

DOI: 10.1002/alz.13909 PMID: 38940303
pubmed: 38940303
doi: 10.1002/alz.13909
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : German Federal Ministry of Education and Research (BMBF)
ID : 13GW0479B

Informations de copyright

© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Références

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Auteurs

Jonathan Vogelgsang (J)

Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
ORCID: 0000-0001-9326-8193

Niels Hansen (N)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Melina Stark (M)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.

Michael Wagner (M)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.

Hans Klafki (H)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Barbara Marcos Morgado (BM)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Anke Jahn-Brodmann (A)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Björn Schott (B)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Hermann Esselmann (H)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Chris Bauer (C)

MicroDiscivery GmbH, Berlin, Germany.

Johannes Schuchhardt (J)

MicroDiscivery GmbH, Berlin, Germany.

Luca Kleineidam (L)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.

Steffen Wolfsgruber (S)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.

Oliver Peters (O)

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Luisa-Sophie Schneider (LS)

Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Xiao Wang (X)

Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Felix Menne (F)

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Predemtec AG, Rudower Chausee 29, Berlin, Germany.

Josef Priller (J)

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
School of Medicine, Department of Psychiatry and Psychotherapy, Technical University of Munich, Munich, Germany.
University of Edinburgh and UK DRI, Edinburgh, UK.

Eike Spruth (E)

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Slawek Altenstein (S)

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Andrea Lohse (A)

Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Anja Schneider (A)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.

Klaus Fliessbach (K)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.

Ina Vogt (I)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.

Claudia Bartels (C)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.

Frank Jessen (F)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany.
Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Ayda Rostamzadeh (A)

Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany.

Emrah Duezel (E)

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.

Wenzel Glanz (W)

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.

Enise Incesoy (E)

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.
Department for Psychiatry and Psychotherapy, University Clinic Magdeburg, Magdeburg, Germany.

Michaela Butryn (M)

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.

Katharina Buerger (K)

German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.

Daniel Janowitz (D)

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.

Michael Ewers (M)

German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.

Robert Perneczky (R)

German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy) Munich, Munich, Germany.
Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, South Kensington, London, UK.

Boris Rauchmann (B)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Broomhall, Sheffield, UK.
Department of Neuroradiology, University Hospital LMU, Marchioninistrassee, Munich, Germany.

Selim Guersel (S)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.

Stefan Teipel (S)

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.

Ingo Kilimann (I)

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.

Doreen Goerss (D)

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.

Christoph Laske (C)

German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.

Matthias Munk (M)

German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.

Carolin Sanzenbacher (C)

German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.

Annika Spottke (A)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurology, University of Bonn, Bonn, Germany.

Nina Roy-Kluth (N)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.

Michael Heneka (M)

Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval Esch-sur-Alzette, Luxembourg.

Frederic Brosseron (F)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.

Alfredo Ramierez (A)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.
Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, Texas, USA.

Matthias Schmid (M)

German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany.
Institute for Medical Biometry, University Hospital Bonn, Bonn, Germany.

Jens Wiltfang (J)

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.

Classifications MeSH